The Genetics Behind Oxygen Drop during Sleep

Low oxygen levels during sleep are a clinical indicator of the severity of sleep apnea, dementia, and death. In a study published today in the American Journal of Human Genetics, researchers present 57 variations of a gene that is strongly associated with blood oxygen decline during sleep.

“A person’s average blood oxygen levels during sleep are hereditary, and relatively easy to measure,” says coauthor Susan Redline of Harvard Medical School. “Studying the genetic basis of this trait can help explain why some people are more susceptible to sleep disordered breathing and its related morbidities.”

When we sleep, the oxygen level in our blood drops, due to interruptions in breathing. Lung and sleep disorders tend to decrease those levels further—and dangerously so. But the range of those levels during sleep varies widely between individuals and seems to be greatly influenced by genetics.

The researchers analyzed whole genome sequence data from the NHLBI’s Trans-Omics for Precision Medicine (TOPMed) program. To strengthen the data, they incorporated results of family-based linkage analysis, a method for mapping genes that carry hereditary traits to their location in the genome. The method uses data from families with several members affected by a particular disorder.

The newly identified 57 variants of the DLC1 gene were clearly associated with the fluctuation in oxygen levels during sleep. In fact, they explained almost 1% of the variability in the oxygen levels in European Americans, which is relatively high for complex genetic phenotypes that are influenced by a myriad of variants.

Notably, 51 of the 57 genetic variants “influence and regulate human lung fibroblast cells, a type of cell producing scar tissue in the lungs,” says senior author Xiaofeng Zhu, of the Case Western Reserve University School of Medicine. Zhu says that this is important because “Mendelian Randomization analysis, a statistical approach for testing causal relationship between an exposure and an outcome, shows a potential causal relationship between how the DLC1 gene modifies fibroblasts cells and the changes in oxygen levels during sleep.”

This relationship could suggest that a shared molecular pathway, or a common mechanism, may be influencing a person’s susceptibility to the lack of oxygen caused by sleep-disordered breathing and other lung illnesses such as emphysema.